CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-CAS (CRISPR-associated) genes provide defense against foreign nucleic acids. These systems utilize an array of small CRISPR RNAs (crRNAs) consisting of repetitive sequences flanking spacers to recognize their targets, and certain CAS proteins to mediate targeted degradation. See Hale et al., Cell, 2009, 139, 945-956; Gasiunas et al., Proc Natl Acad Sci USA, 2012, 109, E2579-2586; Jinek et al., Science, 2012, 337, 816-821; and Datsenko et al., Nat Commun, 2012, 3, 945. Garneau et al., Nature, 2010, 468, 67-71, report the CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Barrangou et al., Science, 2007, 315, 1709-1712, report that CRISPR provides acquired resistance against viruses in prokaryotes. Marraffini & Sontheimer, Science, 2008, 322, 1843-1845, report CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA.
Horvath et al., WO2007025097, report the use of one or more Cas genes or proteins for modulating the resistance of a cell against a target nucleic acid or a transcription product thereof.
Hale et al. report essential features and rational design of CRISPR RNAs that function with the Cas RAMP module complex to cleave RNAs. Molecular Cell, 2012 45, 292-302.
Cho et al. report targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nature Biotechnology, 2013, 31, 230-232.
Mali et al. report RNA-guided human genome engineering via Cas9. Science, 2013, 339:823-26. See also Jinek et al., eLife, 2013, 2:e00471.
Nekrasov et al., report targeted mutagenesis in the model plant Nicotiana benthamiana using Cas9 RNA-guided endonuclease. Nat Biotechnol., 2013, 31(8):691-3.
References cited herein are not an admission of prior art.